Vortioxetine and Lewy Body Disorders - Charles M. Lepkowsky, Ph.D - irjpms
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International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
Vortioxetine and Lewy Body Disorders
Charles M. Lepkowsky, Ph.D.
Independent Practice, 1143 Deer Trail Lane, Solvang, CA USA 93463
Telephone: (805) 688-1229
Email: clepkowsky @ gmail.com
Abstract—
Introduction: Vortioxetine is a newer antidepressant medication with reported potential for mitigating cognitive impairment secondary to major
depressive disorder. However, the current study suggests that the use of Vortioxetine for patients with Lewy Body Disorders may present
complications due to its interactions with medications frequently prescribed to that population, including Bupropion and Carbidopa-Levodopa.
Methods: A case study is presented to illustrate Vortioxetine’s potential interactions with Lewy pathology and other medications frequently used
for patients with Lewy Body Disorders. Vortioxetine’s potential for exacerbation of Lewy pathology symptoms including cognitive impairment
and gastric immotility is described, and the underlying biochemical mechanisms are explained.
Results: The use of Vortioxetine exacerbated Lewy Body symptoms including cognitive impairment and gastric immotility. Discontinuation of
Vortioxetine alleviated symptom exacerbation.
Discussion and Conclusions: The chemical mechanisms responsible for symptom changes consequent to Vortioxetine’s interactions with
serotonergic and cholinergic suppression characteristic of Lewy pathology, and other medications used for the Lewy Body patient in the case
study are discussed. The use of Vortioxetine for patients with Lewy Body Disorders may present complications due to its effect on
neurotransmitter pathways affected by Lewy pathology, as well as its interactions with medications frequently prescribed to that population.
Recommendations are made for screening Lewy Body patients before prescribing Vortioxetine.
Keywords— Cognitive Impairment; Constipation; Drug Interactions; Lewy Body Disorders; Parkinson’s Disease; Vortioxetine.
other conditions wherein cognitive impairment is a prominent
I. INTRODUCTION feature [41], prompting the FDA to update Vortioxetine labels
to ―include data showing improvement in processing speed, an
A pproved for use in the U.S. by the FDA in 2013 [1,
2], Vortioxetine is described as both an atypical
antipsychotic and an antidepressant. Intended for
the treatment of major depressive disorder (MDD) [3], it may
important aspect of cognitive function in acute Major
Depressive Disorder (MDD)‖ [5].
C. Mechanisms of Action
have benefit for reduction of anxiety [4] and enhancement of
memory and cognitive performance [5]. The purpose of this Vortioxetine’s mechanism of action is novel, and more
paper is to review the literature on Vortioxetine’s efficacy for complex than that of other antidepressants [42]. Vortioxetine
treating MDD and anxiety, potential for memory is metabolized by cytochrome P450 enzymes (e.g., CYP450
enhancement, mechanisms of action, and specific suitability 2D6) and subsequently by uridine diphosphate
for use with patients diagnosed with Lewy Body disorders. glucuronosyltransferase [43]. Although its direct mechanism
of action is not fully understood, Vortioxetine is thought to act
A. Clinical Trials, Efficacy and Safety, Long-Term Use as a serotonin reuptake inhibitor (SRI), and is classified as a
In clinical trials, Vortioxetine has demonstrated efficacy in serotonin modulator and simulator (SMS). Acting as a partial
reducing the symptoms of depression [4, 6-18] and anxiety [4, agonist of the 5-HT1B receptor, an agonist of 5-HT1A, and an
19, 20], comparing favorably with SNRI’s including antagonist of the 5-HT3, 5-HT1D, and 5-HT7 receptors,
Duloxetine [17, 20-23], Venlafaxine [24], and Desvenlafaxine Vortioxetine is a serotonin (5-HT) transporter (SERT)
[25], atypical antidepressants including Agomelatine [26, 27], inhibitor [44-48].
and SRI’s including Escitalopram, Sertraline, and Vilazodone Achieving significant clinical effects at much lower
[25] for efficacy and safety. Vortioxetine appears to compare serotonin SERT occupancy (inhibition) rates than traditional
favorably with SRIs including Paroxetine for mitigation of SERT inhibitors, Vortioxetine (unlike SRIs) appears to engage
sleep disturbance [28, 29], and may have long-term benefit in additional downstream and non-serotonergic mechanisms that
the treatment of MDD [30, 31]. mediate its antidepressant and domain-specific effects on
cognition [49]. Its interaction with 5-HT-receptor-mediated
B. Memory Enhancement negative feedback mechanisms controlling neuronal activity
Animal research indicates that Vortioxetine enhances increases serotonergic, noradrenergic, dopaminergic,
memory [32], restoring reversal learning [33], increasing cholinergic, histaminergic and glutamatergic
hippocampal synaptic plasticity [34], and improving neurotransmission in brain structures associated with MDD,
recognition memory [35], benefits not found with Fluoxetine its specific antagonism of 5-HT3 receptors reducing 5-HT3
[36], Escitalopram, or Duloxetine [37]. Clinical trials with receptor-mediated excitation of GABA interneurons,
human subjects diagnosed with MDD indicate that consequently increasing hippocampal pyramidal activity [50].
Vortioxetine not only mitigates cognitive impairment as a The downstream mechanisms influencing glutamatergic and
symptom of MDD [37-40], but may improve cognition in
12
Charles M. Lepkowsky, ―Vortioxetine and Lewy Body Disorders,‖ International Research Journal of Pharmacy and Medical Sciences
(IRJPMS), Volume 2, Issue 2, pp. 12-20, 2019.International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
GABAergic neurotransmission are thought to be the basis of α‐synucleinopathy most infamously impairs dopaminergic
Vortioxetine’s memory- and cognition-enhancing effects [51- function producing Parkinsonian symptoms, but can affect all
53]. neurotransmitter pathways [60, 61]. In LBDs, the emergence
of MDD is associated with impairment of multiple
D. Drug Interactions
neurotransmitter pathways, including serotonergic and
Vortioxetine’s numerous and complex mechanisms of noradrenergic pathways [74-76], at a significantly higher rate
action create the potential for complications. Its 5-HT3 than in Alzheimer’s Disease [77]. NCDLB and PD are also
receptor antagonism appears to exert inhibitory effects over characterized by cholinergic neural deficits and functional
the release of norepinephrine (NE) and acetylcholine (ACh) impairment [60, 61, 69-83], which are recognized as
[54], complicating its role in the regulation of mood and symptomatic features of α‐synucleinopathy [73, 83-85]. These
memory. Although Vortioxetine was initially thought to have include motor symptoms, gait dysfunction, dyskinesias,
a relatively low risk for pharmacodynamic drug interactions cognitive deterioration, psychosis, sleep abnormalities,
[50, 55], Vortioxetine peak plasma concentration and systemic autonomic dysfunction, altered olfactory function [86], and
exposure are significantly decreased when Vortioxetine is co- gastric immotility [87, 88].
administered with Rifampicin, a broad cytochrome P450
inducer which accelerates that enzyme’s metabolism of G. Gastric Immobility as a Quantifiable Indicator of
Vortioxetine [56]. α‐synuclein Cholinergic Impairment
Conversely, several CYP450 2D6 inhibitors (which limit Gastric immotility in Lewy Body patients is at least three
CYP450 2D6’s metabolism of Vortioxetine) significantly times as prevalent as it is among the general population [89],
increase Vortioxetine peak plasma concentration and systemic and might be as a universal feature of Lewy Body disorders
exposure. These include Fluconazole, Ketoconazole, [90]. In both PD and NCDLB, α‐synuclein pathology is found
Bupropion, Cinacalcet, Fluoxetine, Paroxetine, Quinidine, in the enteric nervous system [91-103], specifically in the
Ritonavir, and Terbinafine [43, 56]. Because Fluoxetine and myenteric plexus (MP) [71, 72, 104-108] and the colonic
Paroxetine are selective serotonin reuptake inhibitors, additive submucosal plexus (CSMP) [98], which is innervated by the
serotonergic effects with Vortioxetine specifically increase the MP. The MP controls motility of the colon, and 95% of its
risk of serotonin syndrome [57]. Vortioxetine peak plasma innervation is cholinergic [109], indicating that constipation in
concentration and systemic exposure are even greater in NCDLB and PD is the direct consequence of Lewy pathology
combination with the potent CYP450 2D6 inhibitor Bupropion in the MP. The presence of α‐synuclein aggregates in the MP
[43]. When co-administered, Levodopa-Carbidopa (Sinemet) and its symptomatic manifestation as constipation predate
also significantly increases Vortioxetine peak plasma cognitive and motor symptoms of Lewy body diseases [101,
concentration and systemic exposure [58, 59]. 108] so consistently that it has been nominated as a potential
E. Lewy Body Disorders: Prevalence biomarker for Lewy pathology [110]. Constipation is of
Lewy body disorders are gaining prominence in the particular interest because it is the symptom of cholinergic
research literature, as their diagnostic criteria become more impairment most immediately apparent to the patient and care
defined, making more apparent their increasing prevalence givers [70], and frequency of bowel movements is a
[60, 61]. In 2017, 50 million people worldwide were quantifiable indicator of cholinergic impairment in Lewy body
diagnosed with neurocognitive disease, a figure expected to patients [111].
exceed 75 million by 2030, and 131.5 million by 2050 [62-
64]. Approximately 22% of these diagnoses are assigned to H. Medications Used to Treat Lewy Body Patients
Neurocognitive Disorder with Lewy Bodies (NCDLB) The importance of pharmacological facilitation of
(previously called Lewy Body Dementia) and 9% to serotonergic and dopaminergic systems to address motor and
Parkinson’s disease (PD) [65]. The prevalence of Lewy Body depressive symptoms impaired by α‐synucleinopathy is well
disorders (LBDs) is expected to increase from 15.5 million documented [112, 113]. Antidepressants with evidence-based
people worldwide today to over 40 million by year 2050 [64, application for treating depression in LBD patients include the
66-67]. These figures are likely to grow, as more accurate tricyclics Amitriptyline, Nortriptyline, and Desipramine,
diagnosis decreases the frequent misdiagnosis of LBDs [68]. which may be contraindicated due to their anticholinergic
characteristics, SRIs including Citalopram, Sertraline,
F. α‐synucleinopathy Paroxetine, and Fluoxetine, SNRIs including Venlafaxine, and
Both PD and NCDLB are characterized by the the atypical antidepressant Bupropion [114-117].
intraneuronal presence of Lewy bodies, pathologic aggregates In order to preserve gait, balance, and other basic motor
of the synaptic protein α‐synuclein [69, 70]. functions, Lewy body patients with significant Parkinsonian
α‐synucleinopathy is not confined to the central nervous features are often prescribed L-dopa agents like Carbidopa-
system (CNS), but also affects the autonomic nervous system Levodopa (branded as Sinemet or Stalevo). [70, 118, 119].
(ANS), the peripheral nervous system (PNS) and the enteric ENS α‐synucleinopathy can be complicated or exacerbated by
nervous system (ENS), spreading from one nervous system Carbidopa-Levodopa, whose potential side effects include
area to another over time [71, 72]. Lewy bodies aggregate not constipation [120-123]. Anticholinergic agents including
only near the nucleus of the neuron, but even more abundantly Trihexyphenidyl (branded as Artane or Trihex) and
in neurites (axons and dendrites) [73]. Benztropine mesylate (branded as Cogentin) prescribed to
13
Charles M. Lepkowsky, ―Vortioxetine and Lewy Body Disorders,‖ International Research Journal of Pharmacy and Medical Sciences
(IRJPMS), Volume 2, Issue 2, pp. 12-20, 2019.International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
reduce resting tremor in Lewy body patients can also suppression, whose symptomatic expression paradoxically
exacerbate gastric immotility through cholinergic suppression includes cognitive deterioration, as well as motor and gait
in the ENS. [119, 124-126]. dysfunction, dyskinesias, psychosis, sleep abnormalities,
altered olfactory function [86], and autonomic dysfunction,
I. Medications Used to Treat Cholinergic Impairments in
including gastric immotility [87, 88]. Gastric immotility’s
Lewy Body Patients
advancement from constipation to obstipation and impaction
Cholinergic agonists like acetylcholinesterase inhibitors complicate treatment by interfering with mobility, sleep,
(AChEIs) are often used for symptomatic relief of cholinergic cognition, and mood, increase the cost of care, and can
impairment attributable to α‐synuclein pathology [74, 86, 127- debilitate and/or dramatically reduce the quality of life for the
129]. For the treatment of LBD cognitive impairment, the patient [143-149]. Exacerbation of α‐synuclein cholinergic
cholinergic agonist Donepezil (Aricept) compares favorably suppression consequent to the use of Vortioxetine in
with other AChEIs including Galantamine and Rivastigmine, combination with Bupropion is illustrated in the following
improving cognition [130], but with fewer side effects [131]. case study, for which an Institutional Review Board has
Significant improvements in cognition and behavior following granted a waiver.
administration of Donepezil disappear when Donepezil is
withdrawn, and return when Donepezil is readministered II. METHODS
[132]. In a 52-week study, long-term cognitive improvement For the purpose of illustrating potential interactions
was maintained in LBD patients with regular use of between Vortioxetine and other medications frequently used to
Donepezil, with no increase in Parkinsonian features or other treat patients diagnosed with Lewy Body disorders, a case
clinically significant events. [133, 134]. study was selected using pre-existing deidentified records
Other symptoms of α‐synuclein cholinergic impairment originally collected for clinical purposes.
including hallucinations, delusions, and psychotic symptoms
in PD patients have been reduced using Donepezil, without the A. Case Study
emergence of other side effects or exacerbation of Mr. C. was a white male between 65 and 70 years of age
Parkinsonian features [135, 136]. Donepezil’s efficacy for diagnosed with Neurocognitive Disorder with Lewy Bodies
consistent reduction of neurocognitive symptoms in PD & (NCDLB). His symptoms were characteristic of Lewy Body
NCDLB without exacerbation of Parkinsonian features or α-synucleinopathy, including late-life onset major depressive
other side effects has been confirmed by a Cochrane database disorder (MDD), anxiety, motor abnormalities (tremor,
systematic review of previous research [137] and reproduced weakness), gait dysfunction, dyskinesias, cognitive
in subsequent research [138, 139]. Donepezil’s support of deterioration including short-term memory loss and difficulty
cholinergic neurotransmitter pathways to counter alpha- word-finding, sleep abnormalities including REM Sleep
synuclein cholinergic impairment in the MP and the CSMP Behavior Disorder (RSBD) and REM Sleep without Atonia
reducs constipation in LBD patients, without exacerbation or (RSWA), and autonomic dysfunction including appetite
instigation of other symptoms [111]. Longitudinal case studies suppression and gastric immotility, which had progressed over
indicate that these benefits endure over 6, 12, and 18 month the preceding two years from constipation to obstipation to
periods [140, 141, 142]. impaction. His frequency of bowel movements was about once
a week, with periodic decreases infrequency. He had been
J. Vortioxetine and LBD Patients
hospitalized three times during the previous year for treatment
Frequently prescribed to LBD patient for containment of of impaction. Screening using the Mini-Mental State Exam
Parkinsonian features, Levodopa-Carbidopa (Sinemet) (MMSE) [150], the Quick Dementia Rating Scale (QDRS)
significantly increases Vortioxetine peak plasma concentration [151], and the Lewy Body Composite Risk Score (LBCRS)
and systemic exposure, requiring significant reductions of [152] indicated mild cognitive impairment (MCI) and
Vortioxetine dosages and close monitoring [58, 59]. Often neurocognitive impairment consistent with Lewy body
prescribed to LBD patients for management of MDD diseases.
symptoms, the SRI’s Fluoxetine and Paroxetine are CYP450 The patient’s medication regimen included Bupropion 75
2D6 inhibitors, which co-administered with Vortioxetine can mg HS, 50 mg QHS, Clonazepam 0.325 mg QHS,
produce additive serotonergic effects with the risk of serotonin Aripiprazole 5 mg QHS, Melatonin 6 mg QHS PRN,
syndrome [43, 56]. Also used to treat depression in LCDs, Mirtazapine 30 mg QHS, Carbidopa-Levodopa 25/100 mg
Bupropion is a potent CYP450 2D6 inhibitor, and co- TID, Memantine 10 mg BID. Bupropion and Aripiprazole had
administered with Vortioxetine can more than double its peak been prescribed to address the MDD; Clonazepam for anxiety;
plasma concentration and systemic exposure [56, 57]. Melatonin and Mirtazapine for sleep assistance, with the
Frequently used to address sleep impairment in LBD patients, intention that Mirtazepine might also mitigate the MDD;
tricyclic antidepressants multiply Vortioxetine’s Memantine for cognitive impairment; and Carbidopa-
anticholinergic effects [53], demonstrated with Amitriptyline, Levodopa for gait disturbance and other motor symptoms.
Nortriptyline, and Desipramine [73]. The prescriptions appeared to improve mood, motor
In LBD patients, amplified cholinergic suppression function, and cognitive function, but there was no change in
consequent to the use of Vortioxetine in combination with RSBD/RSWA or the frequency of bowel movements. To
tricyclics or Bupropion can exacerbate α‐synuclein cholinergic address the symptom of constipation and possibly further
14
Charles M. Lepkowsky, ―Vortioxetine and Lewy Body Disorders,‖ International Research Journal of Pharmacy and Medical Sciences
(IRJPMS), Volume 2, Issue 2, pp. 12-20, 2019.International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
improve cognitive functioning, the patient was prescribed apparently exacerbating Lewy Body α‐ synuclein cholinergic
Donepezil 2.5 mg daily. Within two weeks, the frequency of suppression in the ENS.
bowel movements had increased to every other day. The Although believed to bind in the same binding site,
patient stated dissatisfaction with his bowel production and Vortioxetine’s serotonergic inhibitory mechanism varies from
appetite, so the dosage of Donepezil was increased to 5 mg classical 5-HT3 receptor competitive antagonists. After partial
daily, and four weeks later to 10 mg daily, with subsequent agonist activity, Vortioxetine demonstrates what has been
improvements in appetite, intake, and bowel output volume. described as ―a persistent and insurmountable inhibition‖
The patient’s frequency of bowel movements increased to [153]. The molecular mechanisms underlying Vortioxetine’s
once a day, without increasing Parkinsonian features or other site binding appear to be different from currently known 5-
clinically significant symptoms. The patient and his spouse HT3Aorthosteric ligands. In addition to binding in a manner
reported concurrent significant improvement in short-term that resemble the setron class of competitive antagonists and
memory, word finding, and general cognitive functioning. 5-HT, interacting with residues of the aromatic box motif in
Retesting with the MMSE, the QDRS and the LBCRS verified the orthosteric binding site, Vortioxetine additionally interacts
these reports. These results remained stable when reassessed at with residues not previously described to be important for the
intervals of 6, 12, and 18 months [140, 141, 142]. binding of either setrons or 5-HT, including Thr176 on loop B
18 months after initiation of treatment with Donepezil, the and Val202 on loop F [153]. As Vortioxetine’s peak plasma
patient stated increased depression, and (in addition to other concentration and systemic exposure can be more than
medications reported above) was prescribed Vortioxetine 10 doubled by its combined interactions with Bupropion and
mg daily. Within two weeks, the patient reported that the Levodopa-Carbidopa [43, 58, 59], its serotonergic inhibitory
frequency of bowel movements had dropped to once a week or potential is also significantly increased. In the case study, it
less. He was taken to the Emergency Room at the hospital and appears that the combination of Vortioxetine’s serotonergic
was treated for impaction after 10 days without a bowel and cholinergic inhibition significantly interfered with
movement. The patient also complained of increased cognitive cognition.
impairment (confusion, difficulty with calculations, task Vortioxetine also has potential for interaction with other
completion, and word-finding). Discussion with the antidepressants with evidence-based application for treating
prescribers led to a consensus that the dramatic reductions in depression in LBD patients. These include the tricyclics
cognitive function and gastric motility manifested as reduction Amitriptyline, Nortriptyline, and Desipramine, SRIs including
in frequency of bowel movements were likely the result, Citalopram, Sertraline, Paroxetine, and Fluoxetine, SNRIs
respectively, of serotonergic inhibition, and exacerbation of including Venlafaxine, and the atypical antidepressant
α‐ synuclein cholinergic suppression consequent to the use of Bupropion [114-117]. Fluoxetine and Paroxetine are potent
Vortioxetine in combination with Bupropion and Levodopa- CYP450 2D6 inhibitors, and Fluoxetine’s inhibitory effects on
Carbidopa. The use of Vortioxetine was discontinued, CYP-activity can persist for several weeks after fluoxetine
although the use of Bupropion and other medications discontinuation because of the long half-life of fluoxetine and
continued. its metabolite Norfluoxetine, which similar to Sertraline is a
moderate CYP2D6 inhibitor [154]. CYP450 2D6 inhibition
III. RESULTS lends these medications potential for increasing the peak
The patient reported that about 24 following plasma concentration and systemic exposure of Vortioxetine,
discontinuation of Vortioxetine, gastric motility had resumed, increasing not only Vortioxetine’s potential for cholinergic
with a bowel movement. Within 48 hours, the frequency of suppression, but also increasing the risk of serotonin syndrome
bowel movements returned to once daily, and the patient and when it is co-administered with SRI’s and SNRI’s. The
his spouse reported a return to pre-Vortioxetine levels of tricyclics Amitriptyline, Nortriptyline, and Desipramine have
cognitive functioning. There were no other changes in the anticholinergic side effects, which can also potentiate
patient’s symptoms. The patient’s symptom picture has Vortioxetine’s potential for cholinergic suppression when co-
remained constant during the six months since the administered with Vortioxetine.
discontinuation of Vortioxetine. The drug interactions described above and illustrated in the
case study suggest that the use of Vortioxetine with LBD
IV. DISCUSSION AND CONCLUSIONS patients might present complications, if not risks. There are
The case study serves as a quantifiable demonstration of numerous other prescriptive and over the counter (OTC)
Vortioxetine’s potential for serotonergic and cholinergic medications with anticholinergic effects frequently used by
inhibition, and importantly, its reversibility. As a potent this population, including but not limited to Alimemazine
CYP450 2D6 inhibitor, Bupropion interferes with the (Theralen), Amantadine (Symmetrel), Alverine (Spasmonal),
metabolism of Vortioxetine, resulting in significant increases Belladona (Multiple), Amoxapine (Asendin), Alprazolam
in Vortioxetine peak plasma concentration and systemic (Xanax), Aripiprazole (Abilify), Asenapine (Saphris),
exposure [43]. Levodopa-Carbidopa also significantly Carbamazepine (Tegretol), Atropine (Sal-Tropine), Atenolol
increases Vortioxetine peak plasma concentration and (Tenormin), Cyclobenzaprine (Flexeril), Benztropine
systemic exposure [58, 59]. As illustrated by the case study, (Cogentin), Brompheniramine maleate (Bromax),
the combined interaction of Bupropion and Levodopa- Cyproheptadine (Periactin), Brompheniramine (Dimetapp),
Carbidopa with Vortioxetine can be dramatic, in this instance Carbinoxamine (Histex, Carbihist), Captopril (Capoten),
15
Charles M. Lepkowsky, ―Vortioxetine and Lewy Body Disorders,‖ International Research Journal of Pharmacy and Medical Sciences
(IRJPMS), Volume 2, Issue 2, pp. 12-20, 2019.International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
Cetirizine (Zyrtec), Chlorpheniramine (Chlor-Trimeton), necessary before stronger conclusions can be drawn about the
Chlorthalidone (Diuril, Hygroton), Chlorpromazine appropriateness of Vortioxetine for specific populations.
(Thorazine), Cimetidine (Tagamet), Clemastine (Tavist),
Clidinium (Librax), Clomipramine (Anafranil), Clorazepate LIST OF ABBREVIATIONS
(Tranxene), Clozapine (Clozaril), Codeine (Contin), Major depressive disorder (MDD)
Colchicine (Colcrys), Darifenacin (Enablex), Desloratadine Serotonin Reuptake inhibitor (SRI)
(Clarinex), Dicyclomine (Bentyl), Diazepam (Valium), Serotonin and Norepinephrine Reuptake inhibitor (SNRI)
Dimenhydrinate (Dramamine), Digoxin (Lanoxin), Food and Drug Administration (FDA)
Cytochrome P450 enzymes (e.g., CYP450)
Diphenhydramine (Benadryl), Dipyridamole (Persantine),
Serotonin modulator and simulator (SMS)
Doxepin (Sinequan), Doxylamine (Unisom), Disopyramide Five Hydroxy-Tryptophan (5-HT)
phosphate (Norpace), Fentanyl (Duragesic, Actiq), Serotonin (5-HT) transporter (SERT)
Fesoterodine (Toviaz), Flavoxate (Urispas), Fluvoxamine Gamma Amino Butyric Acid (GABA)
(Luvox), Furosemide (Lasix), Haloperidol (Haldol), Norepinephrine (NE)
Hydralazine (Apresoline), Hydrocortisone (Cortef, Cortaid), Acetylcholine (ACh)
Hydroxyzine (Atarax, Vistaril), Hyoscyamine (Anaspaz, Acetylcholinesterase (AChE)
Levsin), Iloperidone (Fanapt), Imipramine (Tofranil), Acetylcholinesterase inhibitor (AChEI)
Isosorbide (Isordil, Ismo), Loperamide (Immodium), Neurocognitive Disorder with Lewy Bodies (NCDLB)
Parkinson’s disease (PD)
Loratadine (Claritin), Loxapine (Loxitane), Meclizine
Lewy Body disorders (LBDs)
(Antivert), Meperidine (Demerol), Methocarbamol (Robaxin), Central nervous system (CNS)
Methotrimeprazine (Levoprome), Metoprolol (Lopressor, Autonomic nervous system (ANS)
Toprol), Molindone (Moban), Morphine (Contin, Avinza), Peripheral nervous system (PNS)
Nefopam (Nefogesic), Nifedipine (Procardia, Adalat), Enteric nervous system (ENS)
Oxcarbazepine (Trileptal), Olanzapine (Zyprexa), Myenteric plexus (MP)
Orphenadrine (Norflex), Oxybutynin (Ditropan), Perphenazine Colonic submucosal plexus (CSMP)
(Trilafon), Pimozide (Orap), Prednisone (Deltasone, Rapid Eye Movement (REM)
Sterapred), Procyclidine (Kemadrin), Promazine (Sparine), REM Sleep Behavior Disorder (RSBD)
REM Sleep without Atonia (RSWA)
Promethazine (Phenergan), Propentheline (Pro-Banthine),
Mini-Mental State Exam (MMSE)
Propiverine (Detrunorm), Quetiapine (Seroquel), Quinidine Quick Dementia Rating Scale (QDRS)
(Quinaglute), Ranitidine (Zantac), Risperidone (Risperdal), Lewy Body Composite Risk Score (LBCRS)
Scopolamine (Transderm Scop), Solifenacin (Vesicare),
Theophylline (Theodur, Uniphyl), Thioridazine (Mellaril), DECLARATIONS
Tolterodine (Detrol), Trazodone (Desyrel), Triamterene Ethics approval and consent to participate: The Santa Barbara
(Dyrenium), Trifluoperazine (Stelazine), Trihexyphenidyl Cottage Hospital Institutional Review Board granted a waiver
(Artane), Trimipramine (Surmontil), Trospium (Sactura), and (##18-81ix) for this case study.
Warfarin (Coumadin) [119]. By no means exhaustive, this list Consent for publication: A completed consent for publication
gives some idea of the broad range of prescriptive and non- form for the case study is on file with the author.
prescriptive medications with potential to interact with Availability of data and materials: Data sharing is not
Vortioxetine to suppress cholinergic function. Because many applicable to this article as no datasets were generated or
of these medications are non-prescriptive, the possibility that analyzed during the current study.
prescribers might be unaware of their use increases the risk of Competing interests: There are no competing interests
potential interaction with Vortioxetine. involved in the research reported or the writing of this paper.
Complicating the prescription picture, LBD patients are Funding: This research received no specific grant from any
often simultaneously medicated by an internist, a psychiatrist, funding agency in the public, commercial or not-for-profit
a neurologist, a movement specialist, and possibly other sectors.
specialists (e.g., gastroenterologist, urologist). [70]. Difficulty Authors' contributions: This paper was written according to
coordinating ongoing communication between prescribers in the Ethical Principles of the American Psychological
siloed care settings creates greater potential risk for dangerous Association. Charles M. Lepkowsky, Ph.D. is the sole author
drug interactions [155, 156]. At this time, it appears that the of this work, including its conception and design; the
use of Vortioxetine for patients diagnosed with Lewy Body acquisition, analysis, and interpretation of data; drafting,
disorders might present numerous risks. However, writing, and editing; final approval of the version published;
Vortioxetine is a relatively new medication, and as indicated and accepts accountability for all aspects of the work in
above, research to date has produced results that are not ensuring that questions related to the accuracy or integrity of
entirely consistent. Risks can be mitigated by ongoing close any part of the work are appropriately investigated and
communication between prescribers, which is recommended resolved.
for the use of Vortioxetine, as well as any other medication for Acknowledgements: There are no acknowledgements pertinent
LBD patients. Further research with larger data sets matching to this case study.
groups for diagnosis, age, gender, and other variables will be
16
Charles M. Lepkowsky, ―Vortioxetine and Lewy Body Disorders,‖ International Research Journal of Pharmacy and Medical Sciences
(IRJPMS), Volume 2, Issue 2, pp. 12-20, 2019.International Research Journal of Pharmacy and Medical Sciences
ISSN (Online): 2581-3277
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